EMR200147-500: A prospective, randomized, placebo-controlled, double-blind clinical trial to evaluate whether EGRIFTA(RegisteredTM) (tesamorelin for injection), 2 mg once daily SC, increases the risk of development or progression of diabetic retinopathy when administered to HIV-infected subjects with abdominal lipohypertrophy and concomitant diabetes
This is a double-blinded study that uses a stratified, 2-arm, parallel group design with a placebo control and is randomized 2:1 (EGRIFTA(TM) to placebo) treatment allocation. Subjects will be screened for participation up to 4 weeks prior to randomization. At baseline, certain entry criteria will be rechecked and baseline laboratory and safety assessments will be conducted. Subjects will be stratified by the presence or absence of DR and HbA1c level (6.0% to 8.0% vs. and amp;gt;8.0% to 12.0%) prior to randomization.
Participants that decide to participate in this study will be assigned to 1 of the 2 groups:
Group A: EGRIFTA(TM), 2 mg once a day
Group B: Placebo once a day
Following randomization, subjects will return to the clinic for 15 study visits.
The difference in percentages of subjects with a 3-step or greater progression (from both eyes) on the ETDRS PERSON scale between subjects treated with EGRIFTA(TM) vs. those treated with placebo.
Difference in percentages of subjects with a 3-step or greater progression in at least one eye on the ETDRS EYE scale in subjects treated with EGRIFTA(TM) vs. those treated with placebo;
Time from first dose to the first assessment of a 3-step progression on the ETDRS PERSON scale in subjects treated with EGRIFTA(TM) vs. those treated with placebo;
Association of IGF-1 levels with progression of DR in subject treated with EGRIFTA(TM);
Change from baseline in HbA1c by intensification of concomitant diabetic treatment (yes or no) within each treatment arm. Subjects are defined as having concomitant treatment intensification if any of the following conditions are met:
a) starting a pharmacologic treatment;
b) adding a medication, including OHA, GLP-1 analogue, or insulin;
c) increasing total daily dose of insulin by at least 20%;
Incidence of MACE in subjects treated with EGRIFTA(TM) versus placebo;
Percentage of subjects who require treatment for DR during the study and the percentage who require each type of treatment, such as laser photocoagulation, intravitreal injection, or vitrectomy.
1. Subject has given written informed consent;
2. Subject is an adult man or woman (>= 18 years old);
3. Subject has laboratory confirmed HIV infection;
4. Subject is receiving ART that has been stable for at least 8 weeks prior to screening;
5. Subject has physical evidence of abdominal lipohypertrophy, as determined by the examining study physician;
6. Subject has T2DM as determined by previous HbA1c >= 6.5%, previous fasting plasma glucose (FPG) >= 126 mg/dL (7.0 mmol/L), and/or previous 2-hour plasma glucose >= 200 mg/dL (11.1 mmol/L) during oral glucose tolerance testing (OGTT), and/or previous random plasma glucose >= 200 mg/dL (11.1 mmol/L) with symptoms of uncontrolled DM; if subject has been diagnosed with T2DM and is on glucose lowering medications for greater than 1 year the above glucose parameters do not apply;
7. Subject, at the time of screening, has HbA1c between 6.0% and 12.0%; Individuals who
are on a stable dose (at least 3 months) of insulin, an OHA, or a GLP-1 analogue plus insulin to control diabetes are permitted if their HbA1C is below 6.0%
8. Subject[Single Quote]s diabetes has been treated for at least 1 year by diet alone, insulin alone, OHA, GLP-1 analogue, or OHA/GLP-1 analogue plus insulin according to current American Diabetes Association (ADA) guidelines, and doses have been stable for at least 3 months;
9. If the subject is using lipid lowering drugs, the dose must be stable for at least 2 months prior to screening;
10. Subject must have an electrocardiogram (ECG) without clinically significant abnormalities within 6 months prior to screening;
11. Pre-menopausal women of childbearing potential are eligible only if they are not pregnant (negative urine pregnancy tests at screening and baseline) or lactating and are using an acceptable form of birth control prior to study entry and for at least 2 months after completing treatment. Acceptable contraception is defined as two barrier methods, or one barrier method with a spermicide, or an intrauterine device, or an oral contraceptive;
12. Women of non-childbearing potential must be post-menopausal (no menses for more than 1 year) or surgically sterile (tubal ligation or hysterectomy);
13. Women over 40 years old must have a negative mammogram within 6 months prior to
screening or a mammogram will be taken at screening;
14. Men must have a normal prostate exam and for men 50 years of age or older, a prostate specific antigen (PSA) <= 5 ng/mL within 6 months prior to screening or PSA will be measured at screening.